This is a continuing study of enzymatic drug+acetylation, a major route of inactivation of drugs in man prior to their elimination from the body. Genetic and environmental factors are influential in regulating this process and contribute to the toxicity of drugs such as isoniazid, various sulfonamides and dapsone and of aromatic amines with carcinogenic potential such as aminogluorene and beta-naphthylamine. Our program makes use of biochemical and genetic techniques to evaluate factors which act to maintain constant levels of these enzymes in tissues and which can modify their activity. Procedures for purifying and characterizing those enzymes have been developed. It is our goal to characterize variant forms of these enzymes and to identify factors which can modify their activity from in vitro studies of human tissues and in vivo and in vitro studies in animal models. Knowledge of these properties has advanced our understanding of this enzyme system in drug inactivation and has shown that differences in the molecular properties of these enzymes underlie inherited differences in the acetylation of aromatic amine drugs and other aromatic amines.